Putting Vaccine Benefits and Risks into Perspective for Patients and Parents

Putting Vaccine Benefits and Risks into Perspective for Patients and Parents

Material authored by:Gary S. Marshall, MDProfessor of PediatricsChief, Division of Pediatric Infectious DiseasesDirector, Pediatric Clinical Trials UnitUniversity of Louisville School of MedicineLouisville, Kentucky

From Fear of Disease to Fear of Adverse Events

Salk J. Pediatr Infect Dis J. 1987;6:889-893.Infectious Disease News; November, 1998.

National Vaccine Information CenterGeneration RescueConcerned Parents For Vaccine SafetyCitizens for Healthcare FreedomVaccine Information Resource CenterPAVE: People Advocating Vaccine EducationFuture GenerationsVaccination AlternativesNatural Immunity Information NetworkAge of AutismHealthy AlternativesThe Canary PartySafe MindsThinkTwice Global Vaccine Institute

A Sampling of Anti-Vaccine Groups

Marshall GS. The Vaccine Handbook. PCI Books, Inc.; 2012.

Undervaccinated UnvaccinatedBlack WhiteYoung, unmarried mother without college degree

Married mother with college degree

Near poverty level Annual income > $75,000Live in central city Live in states with

philosophical exemptionsClaim doctors have little influence over vaccination decisions

Smith PJ, et al. Pediatrics 2004;114:187-195.

Who Are the Vaccine Protestors?

1. Vaccines are good for public health

Immunization Truths

DiseaseHistorical Peak 2004-2006

Cases Deaths Cases Deaths

Diphtheria 30,508 3,065 0 0Measles 763,094 552 55 0Mumps 212,932 50 6,584 0Pertussis 265,269 7,518 15,632 27Poliomyelitis (acute) 42,033 2,720 0 0Poliomyelitis (paralytic) 21,269 3,145 0 0Rubella 488,796 24 11 0Congenital rubella synd 20,000 2,160 1 0Smallpox 110,672 2,510 0 0Tetanus 601 511 41 4

Vaccine Programs Initiated Before 1980

Roush SW, et al. JAMA. 2007;298:2155-2163.

DiseaseHistorical Peak 2004-2006

Cases Deaths Cases† Deaths†

Hepatitis A 254,518 298 15,298 18

Hepatitis B 74,361 267 13,169 47

Hib (invasive) > 20,000 > 1,000 < 50 < 5

Pneumo (invasive) 64,400 7,300 41,550 4,850

Varicella 5,358,595 138 612,768 19†Estimates

Vaccine Programs Initiated After 1980

Roush SW, et al. JAMA. 2007;298:2155-2163.

Infant feedingChildhood safety

Folic acidDiet

Alcohol and drugsNewborn screening

Physical activityAdolescent tobacco

Breast cancerColorectal cancer

Cervical cancerChildhood immunizations

0 50 100 150 200 250 300 350 400 450 500

QALYs Saved x 1000

Impact of Childhood Vaccinations

Coffield AB, et al. Am J Prev Med. 2001;21:1-9.

VaccinePrograms†

2001 Birth Cohort (N = 3,803,295)

Cases Deaths Total Costs

Without 14,330,376 33,564 $46,557 mil

With 708,372 463 $482 mil†DTaP, Hib, IPV, MMR, HepB, varicella (not included: rotavirus, HepA, PCV-7, influenza, MCV-4, HPV)

$1 spent = $5 in direct medical costs$11 in societal costs

Impact of Childhood Vaccinations

Zhou F, et al. Arch Pediatr Adolesc Med. 2005;159:1136-1144.

1. Vaccines are good for public health2. Public concern about vaccines is pervasive

Immunization Truths

Vaccines are a good way to protect children 90%

Generally follow doctor’s recommendations 88%

Concerned about adverse effects 54%

Vaccines cause autism 25%

Personally know someone harmed by MMR 40%

Refused at least one recommended vaccine 12%

Parental Concerns About Vaccines

Freed GL, et al. Pediatrics. 2010;125:654-659.

Newsweek. July 31, 2000Time. June 2, 2008

Public Concern Is Pervasive

1. Vaccines are good for public health2. Public concern about vaccines is pervasive3. Fear of vaccines can lead to public harm

Immunization Truths

0

500

1940 19901965

Vaccineuptake81%

31%93%

Inci

denc

e pe

r 100

,000

Incidence of Pertussis:England and Wales

Gangarosa EJ, et al. Lancet. 1998;351:356-361.

Disease Risk

Attributable Risk Among

Refusers

Attributable Risk in

Population

Pertussis 23-times higher 99.5% 11%

Varicella 9-times higher 99.4% 5%

Case Control Studies

Glanz JM, et al. Pediatrics. 2009;123:1446-1451. Glanz JM, et al. Arch Pediatr Adol Med. 2010;164:66-70.

Data from Kaiser Permanente, Colorado (1996-2008)

2000 2010

Wakefield AJ, et al. Lancet. 1998;351:637-641.

1988 1989 1990 1991 1992 19930

5

10

15

20

25

30

35

0

20

40

60

80

100

AutismMMR

Cases per 10,000 Boys

2-5 Yrs

Vaccine Prevalence

(%)

Annual Birth Cohort

MMR and Autism: United Kingdom

Kaye JA, et al. Br Med J. 2001;322:460-463.

1980

1982

1984

1986

1988

1990

1992

1994

0

200

400

600

800

1000

1200

1400

0

20

40

60

80

100AutismMMR by 24 Months

Birth Cohort

CasesVaccine

Prevalence (%)

MMR and Autism: California

Dales L, et al. JAMA. 2001;285:1183-1185.

Population of Denmark

Children born between01/01/91 and 12/31/98

The Past

MMR1,647,504 person-yr

No MMR482,360 person-yr

Danish Cohort Study

Madsen KM, et al. N Engl J Med. 2002;347:1477-1482.



The Past



The Present

Autism: 263ASD: 345

Autism: 53ASD: 77

Danish Cohort Study




The Past



The Present

Autism: 263ASD: 345

Autism: 53ASD: 77

Relative risk:Autism: 0.92 (0.68-1.24)ASD: 0.83 (0.65-1.07)

Danish Cohort Study


2000 2010

Murch SH, et al. Lancet. 2004;363:750.

2000 2010

General Medical Council, 2010. http://www.gmc-uk.org/Wakefield_SPM_and_SANCTION.pdf_32595267.pdf. Accessed March 2012.

Editorial. Lancet. 2010;375:445.

2000 2010

2,00092

MM

R V

acci

ne C

over

age

(%)

Con

firm

ed M

easl

es C

ases

in

Engl

and

and

Wal

es1,400

1,200

1,000

800

600

400

200

0

1,600

1,800

86

84

82

80

78

76

74

72

88

90

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Consequences of Public Fear

Leask J. Nature. 2011;473;443-445. Editorial Team. Eurosurveillance. http://www.eurosurveillance.org/viewarticle.aspx?articleid=18919. Accessed March 2012.

Wakefield paper

1. Vaccines are good for public health2. Public concern about vaccines is pervasive3. Fear of vaccines can lead to public harm4. Vaccines are not 100% safe

Immunization Truths


Pre-Clinical

Center for Biologics Evaluation and

ResearchGood Manufacturing,

Laboratory and Clinical Practices

Phased clinical trials

Restoring Public Confidence


Pre-Clinical





Licensure andRecommendation

FDAACIPAAP

AAFP



Pre-Clinical





Licensure andRecommendation

FDAACIPAAP

AAFP

Post-Marketing

Phase 4 studiesPharmacovigilanceVaccine Adverse Event Reporting SystemVaccine Safety DatalinkCISA NetworkBrighton CollaborationAd-hoc committees


Background rate in general

population

Rate in vaccinated population2-fold higher 10-fold higher 100-fold higher

1 in 10,000 141,000 5,500 5001 in 100,000 1,238,000 53,500 2,5001 in 1,000,000 12,951,500 532,500 23,500Assumes 5% risk of Type I error and power of 90%

How Many Subjects are NeededTo Detect Adverse Events?

Evans D, et al. J Infect Dis. 2009;200:321-328.

1. Vaccines are good for public health2. Public concern about vaccines is pervasive3. Fear of vaccines can lead to public harm4. Vaccines are not 100% safe5. Parents are human

Immunization Truths

OutcomeYes

ExposureYes a

The Power of Box “a”

Offit PA. Immunization Action Coalition Web site.http://www.immunize.org/safety/boxa.pdf. Accessed March 2012.

OutcomeYes No

ExposureYes a bNo c d

The Power of Box “a”

Offit PA. Immunization Action Coalition Web site.http://www.immunize.org/safety/boxa.pdf. Accessed March 2012.

10,000,000pregnant women

get a shot 6 weekslater

16,684have a spontaneous

abortion

10,000,000women


86develop

optic neuritis

Folk Numeracy

Shermer M. Sci Amer. http://www.scientificamerican.com/article.cfm?id=why-our-brains-do-not-intuitively-grasp-probabilities. Accessed January 2012. Black S, et al. Lancet. 2009;374:2115-2122.

10,000,000pregnant women


16,684have a spontaneous

abortion

10,000,000women


86develop

optic neuritis

If the shot is a placebo!

Folk Numeracy

Shermer M. Sci Amer. http://www.scientificamerican.com/article.cfm?id=why-our-brains-do-not-intuitively-grasp-probabilities. Accessed January 2012. Black S, et al. Lancet. 2009;374:2115-2122.

1. Vaccines are good for public health2. Public concern about vaccines is pervasive3. Fear of vaccines can lead to public harm4. Vaccines are not 100% safe5. Parents are human6. People don’t understand vaccinology

Immunization Truths

AgeVaccine

Birth 1mo

2mos

4mos

12mos

6mos

18mos

15mos

24mos

11-12yrs

4-6yrs

14-18yrs

Measles, Mumps,Rubella

MMR

Diphtheria,Tetanus,Pertussis

DTP DTP DTP DTP Td

DTP

Polio OPV OPV OPV(OPV) OPV

1982

Childhood Schedule, 1982

Childhood Schedule, 2012

Vaccine 1960 1980 2000 2012

Smallpox 200Diphtheria 1 1 1 1Tetanus 1 1 1 1Pertussis 3000 3000 5 5Polio 15 15 15 15MMR 24 24 24Hib 2 2Varicella 69 69PCV7/PCV13 8 14HepB 1 1HepA 4HPV4 4Rotavirus 20MCV4 5Influenza 12Total 3217 3041 126 177

Antigen Burden

Offit P. Pediatrics. 2002;109:124-129 Marshall GS. The Vaccine Handbook. PCI Books: 2012.

0 1 2 4 6 12 15 18 19-23 2-3 4-6

HepBRotaDTaPHibPCV7IPVFluMeaslesVaricellaHepA

Alternative Vaccine Schedule

Sears RW. The Vaccine Book. Little Brown & Co. 2007.

Argument The TruthGovernment and pharmaceutical companies conspire to misrepresent data.

There is no evidence of conspiracy.

Natural immunity is better than vaccine-induced immunity.

The cost of natural immunity is the risk of serious disease or death.

Vaccines are not adequately tested for safety.

Vaccines are among the most thoroughly tested pharmaceuticals in the world.

Vaccines are recommended for protection of the public, not individuals.

Individuals benefit from vaccines through both individual and herd immunity.

There is a middle ground between causality and coincidence.

Either vaccines do or don’t cause certain adverse events.

Science fails because it cannot prove that vaccines don’t cause adverse events.

Science can only reject or fail to reject the null hypothesis.

Alternative Vaccine Schedule

Offit P, Moser C. Pediatrics. 2009;123:e164.

1. Vaccines are good for public health2. Public concern about vaccines is pervasive3. Fear of vaccines can lead to public harm4. Vaccines are not 100% safe5. Parents are human6. People don’t understand vaccinology7. It’s all about risk perception

Immunization Truths

What We’re Afraid Of What The Real Risk IsShark attacks (28) Dog bites (4.5 million)Murder (14,180) Suicide (33,289)Death by peanut allergy (50) Death by poisoning (27,531)Death by plane crash (321) Death by car crash (34,017)

Risk Perception

Kalb C, et al. Newsweek. 2010;155(22).

Influenza Varicella Anthrax Smallpox0

10,000

20,000

30,000

40,000 36000

10 0 0

Dea

ths

Estimated Annual Mortality in the US

1. Vaccines are good for public health2. Public concern about vaccines is pervasive3. Fear of vaccines can lead to public harm4. Vaccines are not 100% safe5. Parents are human6. People don’t understand vaccinology7. It’s all about risk perception8. There are vaccine anti-champions

Immunization Truths

US Weekly. Oct 27, 2008

Thimerosal

1975 1980 1985 1990 1995 20000

1

2

3

4

5

2-4

Year

Aut

ism

Inci

denc

e pe

r 10,

000 Age

Thimerosal-containingvaccines removed

Danish Population-Based Study

Madsen KM, et al. Pediatrics. 2003;112:604-606.

Autism in California

Adapted from Schechter R, Grether J. Arch Gen Psychiatry. 2008;65:19-24.

1989 1991 1993 1995 1997 1999 2001 2002 2003

x x x x x x x x x x x

x

Cas

es p

er 1

000

Live

Birt

hs4.5

4.0

3.5

3.0

2.5

2.0

1.5

1.0

0.5

0

Year of Birth

Age of Children, y121110 9

8765

432

Vaccine Trade Name Manufacturer StatusDiphtheria, tetanus, pertussis

InfanrixDAPTACEL

GlaxoSmithKlineSanofi Pasteur

FreeFree

PCV Prevnar 13 Wyeth FreePolio IPOL Sanofi Pasteur FreeHepatitis B RECOMBIVAX HB

Engerix-BMerckGlaxoSmithKline

FreeFree

Hib conjugate ActHIBPedvaxHIBHiberix

Sanofi PasteurMerckGlaxoSmithKline

FreeFreeFree

Hib/Hepatitis B COMVAX Merck FreeMMR M-M-RII Merck Free

Varicella VARIVAX Merck FreeDTaP/Hep-B/IPV Pediarix GlaxoSmithKline FreeInfluenza Fluzone T-free

Fluvirin P-freeFlumist

Sanofi pasteurNovartisMedImmune

Free< 1.0 mcg/0.5 mLFree

Hepatitis A VAQTAHavrix

MerckGlaxoSmithKline

FreeFree

Thimerosal in Vaccines

FDA. http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/UCM096228#t1. Accessed March 2012.

5.6 oz30 mcg

Tripedia*< 0.3 mcg/dose

Mercury Exposure

Yess NJ. J AOAC Intl. 1993;76:36-38.

*Tripedia is no longer available; this example has been used to put exposure risk into perspective

1. Vaccines are good for public health2. Public concern about vaccines is pervasive3. Fear of vaccines can lead to public harm4. Vaccines are not 100% safe5. Parents are human6. People don’t understand vaccinology7. It’s all about risk perception8. There are vaccine anti-champions9. Questions remain

Immunization Truths

Which challenges should be investigated? What about perceived conflict of interest? How do families differ in medical orientation? How should vaccine refusal be handled?

Questions

1. Vaccines are good for public health2. Public concern about vaccines is pervasive3. Fear of vaccines can lead to public harm4. Vaccines are not 100% safe5. Parents are human6. People don’t understand vaccinology7. It’s all about risk perception8. There are vaccine anti-champions9. Questions remain10. Parents have to make a choice

Immunization Truths

RadioDaytime TV

Complementary providerNewspaper

TV newsMagazines

OtherInternet

CDCAAP

FriendsChild's other parent

FamilyChild's provider

0 10 20 30 40 50 60 70 80 90 100

Percent of Parents

Sources of Information About Vaccines

Kennedy A, et al. Pediatrics. 2011;127:S92-S99.

Don’t vaccinate VaccinateDiscredited “scientists” Robust science“Advocacy” groups Authoritative bodiesCelebrities YouVulnerability to disease Protection with minimal risk

Parents Must Make a Choice

Documents

Putting Vaccine Benefits and Risks into Perspective for Patients and Parents